The goal of this project is to produce an integrated map of murine chromosome 16. This map will correlate the positions of transcribed regions with the existing genetic map and produce a physical map of restriction endonuclease cleavage sites spanning the entire chromosome. The map will allow us to answer questions of gene number, overlap in the sets of expressed genes, gene clustering, correlation between physical and genetic maps, and chromosome architecture. The integrated map will be used to isolate the locus for the mouse cerebellar development gene weaver(wv) and the mouse region homologous to that responsible for Down's syndrome. 1. We will assemble a nearly complete mouse chromosome 16-specific genomic library that can be rapidly and repeatedly analyzed by hybridization. 2. We will identify clones of expressed sequences and define their patterns of expression. Of special interest will be sequences expressed in the CNS. 3. To place these sequences on the genetic map, clones of expressed regions will be used to identify RFLP's that distinguish strains of mice. These RFLP's will be used to establish linkage of the cloned expressed sequences with known markers. 4. These cloned sequences will be used to determine a large scale restriction map of chromosome 16. 5. The genetic and transcription maps will be used to identify candidate clones of the wv locus. These will be used to examine mutant ice to identify the wv gene. The wv gene products will be characterized. 6. The integrated maps will be studied with reference to the syntenic region of human chromosome 21 to identify candidates for the critical genes whose aneuploidy is responsible for Down's Syndrome.